Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep

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  • Linda Nicel, Human Reproductive Sciences Unit, Medical Research Council, Edinburgh, United Kingdom
  • Stephen Bishop, The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin Biocentre, United Kingdom
  • Richardo Pong-Wong, The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin Biocentre, United Kingdom
  • Christian Bendixen, Denmark
  • Lars-Erik Holm
  • Stewart Rind, The Macaulay Institute, Aberdeen, United Kingdom
  • Alan McNeilly, QMRI, MRC HRSU, Edinburgh, Denmark
  • Molekylær Genetik og Systembiologi
  • Department of Genetics and Biotechnology
The control of fecundity is critical in determining mammalian offspring survival. It is regulated principally by the ovulation rate, so that primates and large farm species commonly have single offspring. Previously, several mutations have been identified in sheep which increase the naturally low ovulation rate, although in some cases homozygous ewes are infertile. In the present study we present a detailed characterisation of a novel mutation in growth differentiation factor 9 (GDF9), found in Icelandic Thoka sheep. This mutation is a single base change (A1279C) resulting in a non-conservative amino acid change (S109R) in the C-terminus of the mature GDF9 protein, which is normally expressed in oocytes at all stages of development. Genotyping all animals for which reproductive records were available confirmed this mutation to be associated with increased fecundity in heterozygous ewes and infertility in homozygotes. Analysis of homozygote ovarian morphology and a number of genes normally activated in growing follicles showed that GDF9 was not involved in oocyte activation, but in subsequent development of the follicle. This study highlights the importance of oocyte factors in regulating fertility and provides new information for structural analysis and investigation of the potentially important sites of dimerization or translational modifications required to produce biologically active GDF9. It also provides the basis for the utilisation of these animals to enhance sheep production
Original languageEnglish
JournalReproduction
Volume138
Issue6
Pages (from-to)921-933
Number of pages13
ISSN1470-1626
DOIs
Publication statusPublished - 2009

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